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J Med Genet. 2007 August; 44(8): e87.
PMCID: PMC2597940

Phenocopies: actual risk or self‐fulfilling prophecy?

The contribution of Smith et al1 regarding the risk cancer in women who test negative for a known familial BRCA mutation is extremely valuable for both clinicians and researchers, and deserves critical attention. Indeed, not only the current National Institute for Health and Clinical Excellence guidelines but most other statements on inherited risk for breast and ovarian cancer suggest reassurance for relatives found to be free of a familial BRCA mutation. As Smith and colleagues point out, this reassurance might be false or misleading. However, the authors have neglected to consider one explanation for their findings.

Relatives of women with breast cancer undergo mammography screening more often and at an earlier age than women without such a family history.2,3,4 Currently, there is substantial concern and controversy about overdiagnosis of breast cancer resulting from screening.5,6,7 Moreover, this effect could be greater for women known to be from high‐risk families if their mammography studies are subjected to more cautious interpretation, resulting in a higher rate of biopsy. Knowledge of risk could in this way create a self‐fulfilling prophecy.8

Could at least a part of the higher relative risk for breast cancer computed in the study of Smith et al1 be attributable to this phenomenon? Information about how cancer in the phenocopies was discovered (whether by screening or other means) and the size of the tumors at diagnosis would help to evaluate this hypothesis.


I thank Wylie Burke for thoughtful discussions.


Competing interests: None declared.


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